Genetic evidence for SecY translocon-mediated import of two 3 contact-dependent growth inhibition (CDI) toxins

Allison M Jones, Petra Virtanen, Disa Hammarlöf, William J Allen, Ian Collinson, Christopher S Hayes, David A Low*, Sanna Koskiniemi

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
54 Downloads (Pure)


The C-terminal (CT) toxin domains of contact-dependent growth inhibition (CDI) CdiA proteins target Gram-negative bacteria and must breach both the outer and inner membranes of target cells to exert growth inhibitory activity. Here, we examine two CdiA-CT toxins that exploit the bacterial general protein secretion machinery after delivery into the periplasm. A Ser281Phe amino acid substitution in transmembrane segment 7 of SecY, the universally conserved channel forming subunit of the Sec translocon, decreases the cytotoxicity of the membrane depolarizing CdiA-CTo10 EC869 from enterohemorrhagic Escherichia coli. Target cells expressing secYS281F and lacking either PpiD or YfgM, two SecY-auxiliary factors, are fully protected from CDI mediated inhibition either by CdiA-CTo10
EC869 or by CdiA-CTGN05224, the latter being an EndoU RNase CdiA toxin from Klebsiella aerogenes GN05224 that has a related cytoplasm-entry domain. RNase
activity of CdiA-CTGN05224 was reduced in secYS281F target cells and absent in secYS281F ppiD or secYS281F yfgM target cells during competition co-cultures. Importantly, an allele specific mutation in secY (secYG313W) renders ppiD or yfgM target cells specifically resistant to CdiACTGN05224, but not to CdiA-CTo10 EC869, further suggesting a direct interaction between SecY and the CDI toxins. Our results provide genetic evidence of a unique confluence between the primary cellular export route for unfolded polypeptides and the import pathways of two CDI toxins.
Original languageEnglish
Article numbere03367-20
Pages (from-to)1-14
Number of pages14
Issue number1
Publication statusPublished - 2 Feb 2021


  • bacterial competition
  • type V secretion system
  • membrane potential


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